Metacontrast and evoked potentials: a reappraisal.

Stimulation of the parafoveal retina may give rise to visual evoked responses generated in large part by stray light impinging upon the fovea. This effect appears to account for the absence of changes in the visual evoked response to parafoveal stimulation during metacontrast suppression. When the central retina is directly stimulated, the spatiotemporal interactions associated with brightness suppression during metacontrast may be readily demonstrated in a late component of the visual evoked response.

Averaged evoked responses in vigilance and discrimination: a reassessment.

With the use of monopolar recordings for averaged evoked responses, detected signals in a vigilance task are associated with a late positive component which is absent for undetected signals as well as nonsignals. Bipolar recordings obscure the late positive component associated with detected signals. The data suggest that the late positive component represents cerebral processes associated with evaluation of unpredictable changes in stimulation.

A brain event related to the making of a sensory discrimination.

Event-related potentials associated with detected targets in a vigilance task were analyzed in two ways: (i) by sorting the potentials in terms of sequential reaction time bins of 50 milliseconds and (ii) by examining the single trial waveforms. A negative component (N2) covaried in latency with reaction time. These results support the hypothesis that N2 reflects a decision process which controls behavioral responses in sensory discrimination tasks.

Manipulation of event-related potential manifestations of information processing stages.

The timing of two event-related potential components was differentially affected by two experimental variables. The earlier component (NA) was affected by degradation of the stimuli and the later component (N2) by the nature of a classification task. The results support the hypothesis that NA and N2 reflect sequential stages of information processing, namely, pattern recognition and stimulus classification.

Electrophysiologic analysis of regional cortical maturation.

Some issues in the study of human neurobehavioral development are briefly set forth. Attention is called to the limitations of strictly structural and behavioral approaches. The value of correlative morphophysiological and psychophysiological investigations is emphasized. By averaging brain activity with respect to stimuli and motor responses, event-related cortical potentials (ERP) can be reliably detected in the scalp EEG. Longitudinal topographic studies of ERP permit the definition of a sequence of regional cortical maturation during infancy and childhood. We have found that evoked potentials in the three major sensory modalities arise from both primary and secondary projection areas by 30 weeks of conceptional age. Frontocentral responses appear shortly thereafter. Thus, cortical mechanisms show a precocious development of electrogenesis which indicates the possibility for an early environmental impact on brain maturation. In contrast to the evoked potentials, association cortex potentials (ACP) do not seem to appear until early childhood. The behavioral significance of these neuroelectric phenomena is being sought in studies employing techniques which permit the concurrent recording of brain activity and behavioral responses in the waking infant and child. Some of the problems confronting the application of these methods to studies of infants are outlined.

Impairment of early cortical processing in schizophrenia: an event-related potential confirmation study.

Abnormalities of auditory information processing represent a core feature of schizophrenic psychopathology. Event-related potentials (ERP) provide an objective index of the information processing deficits associated with schizophrenia and a tool for investigation of the underlying pathophysiology. The best established abnormality is a decrease in the amplitude of auditory P300. In an "oddball" paradigm, P300 is preceded by a series of earlier, negative-polarity ERP components that index discrete, prior information-processing events. The earliest such component, mismatch negativity (MMN), is elicited whenever a deviant, "oddball" stimulus interrupts a sequence of repetitive standard stimuli. MMN is generated principally within primary auditory cortex or adjacent structures on the superior temporal plane, suggesting that it indexes the earliest cortical event in the cognitive processing of auditory information. In the present study, MMN was studied in a group of 14 chronic schizophrenic subjects relative to 12 age- and IQ-matched normal controls in a passive auditory oddball paradigm in order to test the hypothesis that auditory information processing is impaired in schizophrenia, even at the level of primary sensory cortex. Schizophrenic subjects showed a significant reduction in MMN amplitude relative to controls, with a trend toward a greater deficit on the left than the right side. The finding of impaired MMN generation in schizophrenia suggests that information processing is impaired even at the level of auditory cortex and that the pathophysiological processes underlying information processing dysfunction in schizophrenia are widespread throughout the cortex, rather than limited to high-order association cortex such as prefrontal or mesial temporal cortex.

Return to alertness after brain-stem hemorrhage. A case with evoked potential and roentgenographic evidence of bilateral tegmental damage.

After a 65-year-old man had received anticoagulation therapy for brain-stem ischemia, a large, bilateral pontomesencephalic hemorrhage developed in the ischemic region. He survived a period of being "locked in" to attain a limited functional recovery. When he first became alert, brain-stem auditory evoked potentials and short-latency somatosensory evoked potentials (SEPs) demonstrated bilateral brain-stem damage; computed tomography revealed a bilateral tegmental hematoma. Results of repeated studies changed little as clinical improvement occurred. Recovery from brain-stem hemorrhage is rare, and return of consciousness with bilateral tegmental involvement is even more rare. The short-latency SEPs are useful in defining the extent of brain-stem damage, but they evaluate structures distinct from those regulating consciousness and cannot predict a return to alertness.

Trimodal evoked potentials compared with magnetic resonance imaging in the diagnosis of multiple sclerosis.

Twenty-three patients with the clinical diagnosis of possible multiple sclerosis (MS) were tested with magnetic resonance imaging (MRI) and trimodal evoked potentials. Fourteen patients showed abnormalities on both MRI scans and at least one evoked potential modality (65%). Four patients had normal MRI scans but at least one abnormality on evoked potential testing (17%). One patient had normal triple evoked potentials with an abnormal MRI result. Four patients had normal results on both MRI and triple evoked potential testing; two of these patients were later found to have immunologic abnormalities in the cerebrospinal fluid consistent with the diagnosis of MS. Combined evoked potential testing was found to have a higher sensitivity than MRI in confirming a diagnosis of MS. Three patients with the clinical diagnosis of definite MS were also tested. All these patients showed abnormalities on evoked potential testing, although one patient had a normal MRI result. Of all 26 patients who were studied, 17 showed abnormal MRI results and 21 showed at least one abnormality on evoked potential testing.

Event-related potentials associated with the discrimination of acoustic and semantic aspects of speech.

Analysis of a word's acoustic structure must precede identification of its meaning. Therefore, these aspects of speech processing could be associated with event-related potential (ERP) components that differed in their timing. To identify electrophysiologic indices of the cortical processing of acoustic and semantic features of speech, we recorded ERPs to the random presentation of nonsense or real words in four conditions designed to manipulate the extent to which the speech sounds were processed. In one condition subjects responded to all stimuli; in a second and third, to a designated nonsense or real word; and in the final condition to words within a specified semantic category. To define the cortical activity associated with acoustic processing, ERPs obtained when no discrimination was required were subtracted from those recorded during the identification of a specified speech target. The difference waveforms exhibited a negative potential that began about 50 msec after stimulus onset and lasted about 200 msec. Difference waveforms obtained by subtracting the non-discrimination ERP from those obtained during semantic discrimination exhibited a negative potential with similar onset timing. We concluded that the early negative potential indexed acoustic processes necessary for stimulus identification. To identify potentials associated with determination of a word's meaning, we subtracted the verbal discrimination from the semantic discrimination ERPs. This difference waveform exhibited a later negativity beginning at 150 msec and lasting about 250 msec. This potential may be related to the semantic processing of speech.

Cognitive and neurologic development of the premature, small for gestational age infant through age 6: comparison by birth weight and gestational age.

OBJECTIVE: To compare the neurologic and cognitive outcomes of 129 premature small for gestational age (SGA) infants with 300 premature appropriate for gestational age (AGA) infants through 6 years of age. DESIGN: Infants born at < or = 37 weeks gestational age and < or = 2500 g with birth weight 2 standard deviations or more below the mean birth weight for gestational age were categorized as SGA. Cognitive and neurologic outcomes of SGA and AGA prematures at 1, 2, 3, and 5 and/or 6 years of age were compared when the infants were stratified by gestational age in 2-week intervals or by birth weight in 500-g intervals. The association between SGA/AGA and neurologic status on cognitive outcomes at each age was also examined. RESULTS: SGA infants had significantly poorer cognitive scores at each age when compared with AGA infants of similar gestational ages. Normal neurologic status was more likely at all assessments for the AGA than for SGA infants of comparable gestational age. There were no differences between SGA and AGA children in cognitive or neurologic outcomes at any age when grouped by birth weight. Cognitive impairment was closely associated with neurologic abnormality in both SGA and AGA groups. There was, nevertheless, a significant effect of SGA on cognitive outcome independent of neurologic status at all ages except 3 years. CONCLUSIONS: Irrespective of degree of prematurity, SGA infants are at greater risk for neurodevelopmental impairment than are equally premature AGA infants. The cognitive impairment can be largely, but not entirely, attributed to a higher incidence of neurologic abnormalities in the SGA infants at each gestational age.

Storage of information in transient auditory memory.

This study concerns the manner in which features of auditory stimuli are stored in acoustic memory. Event-related potentials (ERPs) were recorded to sequences of tones in which sequential, infrequent deviant tones were presented in a row, each of which differed from the frequent standard tones along a different stimulus dimension. The object was to determine whether a change in a single feature of a stimulus would have an effect on the entire representation of the standard tone in memory, or only on the representation of the stimulus dimension by which the first deviant differed from the standards. It was found that the amplitude of the mismatch negativity elicited by subsequent deviants was not reduced by the presence of the first deviant, supporting independent storage of features.

Lexical processing of visually and auditorily presented nouns and verbs: evidence from reaction time and N400 priming data.

We investigated two aspects of lexical organization in normal adults employing behavioral and electrophysiological indices of semantic priming, namely: (1) Is there evidence for differential processing of nouns and verbs? (2) Is there evidence for separate systems for processing of orthographic and phonologic representations of words? Reaction time (RT), N400 amplitude and latency were used to examine the effect of semantic priming on lexical access of auditorily and visually presented nouns and verbs. We found that the temporal patterns of primed RTs and N400 latencies differed for nouns and verbs, indicating a functional difference in processing. However, the absence of topographic differences in N400 between nouns and verbs did not support anatomically distinct representations of these word classes. By contrast, a modality-specific topography at N400, in addition to RT and N400 amplitude differences between auditory and visual conditions, supported the proposed separation of the orthographic and phonologic representations of words. The implications of the findings for general theories of lexical organization are discussed.

Visual activation of frontal cortex: segregation from occipital activity.

Studies in primates have found visually responsive neurons that are distributed beyond cortical areas typically described as directly involved in vision. Among these areas are premotor cortex, supplementary motor area, dorsolateral prefrontal cortex and frontal eye fields. Given these findings, visual stimulation would be expected to result in activation of human frontal cortex. However, few human studies have described sensory activations in frontal regions in response to simple visual stimulation. Such studies have classically described event-related potential (ERP) components over occipital regions. The present study sought to further characterize the spatiotemporal dynamics of visually-evoked electrocortical responses elicited by simple visual stimuli using scalp current density measures derived from high-density ERP recordings, with particular emphasis on the distribution of stimulus-related activity over frontal cortex. Hemiretinal stimuli were viewed passively and during a simple ipsi- or contramanual (RT) task. The motor requirement was included to investigate the effects of response preparation on premovement frontal activations. The results indicate early frontocentral activation, particularly over the right hemisphere (peak magnitude 124-148 ms) that is independent of input visual field or motor response requirement, and that is clearly separate in timecourse from the posterior responses elicited by visual input. These findings are in accord with the multiplicity of visual inputs to frontal cortex and are discussed in terms of frontal lobe functions as may be required in these tasks.

Predictability of stimulus deviance and the mismatch negativity.

The purpose of this study was to test the previous report that generation of the mismatch negativity (MMN) component of event-related brain potentials (ERPs) is indifferent to the predictable occurrence of stimulus deviance. A pattern of standards (S) and deviants (D) were delivered in a predictable fashion (SSSSD) at two different speeds (1.3 s and 100 ms). An MMN was obtained to the D position tone at the slow but not the fast pace. These results demonstrate that, unlike the P3 component, the MMN is sensitive to the predictable occurrence of stimulus deviance when the predictability can be detected by the brain within the estimated limits of sensory memory.

Averaged multiple unit activity as an estimate of phasic changes in local neuronal activity: effects of volume-conducted potentials.

A technique for the derivation of digitally-averaged multiple unit activity (MUA) is described. The use of signal averaging instead of analog integration improves the temporal resolution and thus provides a clearer picture of the instantaneous MUA level. MUA recordings have been used in the identification of regions active in the generation of event-related potentials, based in part on the limited volume within which a semi-microelectrode 'sees' action potentials. However, averaged MUA waveforms may be affected by time-locked activity volume-conducted to the electrode site. A theoretical analysis of the magnitude of this effect is presented, along with experimental data in support of its assumptions and predictions. The most important factor is not the absolute size of the volume-conducted potentials, but their magnitude relative to that of the locally-generated MUA. When full-wave rectification is used, volume-conducted activity which is a considerable fraction of the MUA level will not significantly affect the averaged MUA waveform. Half-wave rectification should not be used, as it leads to a much larger effect from small far-field potentials.

Topographic analysis of human cortical potentials preceding self-initiated and visually triggered saccades.

The topography of human brain potentials preceding self-initiated saccadic eye movements was compared with those preceding visually triggered saccades to examine differences in presaccadic activity under different programming requirements. A slow negative shift beginning approximately 650 ms before eye movement and largest in amplitude over the frontal region was recorded only in the self-initiated condition. This potential presumably reflects preparatory activity occurring predominantly within the frontal eye fields. A ramp-like positivity preceding eye movements by 100-250 ms and a sharp positive potential peaking 10-40 ms before saccades were recorded under both conditions. These potentials were of maximum amplitude over the parietal region. In order to examine the extent to which presaccadic enhancement of parietal activity was related to executive or to attentional mechanisms, the presaccadic visual evoked potential components were compared with activity at the same latency when stimuli were counted without saccades or were ignored. Enhancement of parietal potentials was seen both with counting and with saccades, but was greater in the eye movement condition. Occipital enhancement predominated with counting and parietal enhancement with saccades. These findings suggest that attentional and command mechanisms contribute distinct complementary increments in posterior cortical presaccadic activity associated with visually triggered saccades.

The sources and intracerebral distribution of auditory evoked potentials in the alert rhesus monkey.

Average auditory evoked potentials (AEP) to click stimuli were recorded from chronically implanted electrodes in alert rhesus monkeys. The cortical sources of each AEP component were identified on the basis of transcortical polarity inversions. The active loci were limited to the supratemporal plane (STP) and to a region within precentral motor cortex. Small and inconstant responses were generated in the lateral superior temporal gyrus and no locally generated activity was detected in frontal granular cortex. The responses from STP were complex, with early components generated mainly within auditory koniocortex and later components in surrounding regions. Each of these components was volume-conducted widely, both above and below the STP, and they projected onto various regions of dorsolateral surface cort(x. The volume-conducted potentials from the STP summed with the potentials generated in motor cortex to produce a complex resultant waveform. Barbiturate anesthesia abolished all but the primary AEP and reduced the volume-conducted projection of this response at the cortical surface. The configuration and intracranial distribution of the monkey AEP were compared to human intracerebral and scalp AEP recordings.

Tonotopic features of speech-evoked activity in primate auditory cortex.

To further clarify the neural mechanisms underlying the cortical encoding of speech sounds, we have recorded multiple unit activity (MUA) in the primary auditory cortex (A1) and thalamocortical (TC) radiations of an awake monkey to 3 consonant-vowel syllables, /da/, /ba/ and /ta/, that vary in their consonant place of articulation and voice onset time (VOT). In addition, we have examined the responses to the syllables' isolated formants and formant pairs. Response features are related to the cortical tonotopic organization, as determined by examining the responses to selected pure tones. MUA patterns that differentially reflect the spectral characteristics of the steady-state formant frequencies and formant transition onset frequencies underlying consonant place of articulation occur at sites with similarly differentiated tone responses. Whereas the detailed spectral characteristics of the speech sounds are reflected in low frequency cortical regions, both low and high frequency areas generate responses that reflect their temporal characteristics of fundamental frequency and VOT. Formant interactions modulate the responses to the whole syllables. These interactions may sharpen response differences that reflect consonant place of articulation. Response features noted in A1 also occur in TC fibers. Thus, differences in the encoding of speech sounds between the thalamic and cortical levels may include further opportunities for formant interactions within auditory cortex. One effect could be to heighten response contrast between complex stimuli with subtle acoustical differences.

Attention affects the organization of auditory input associated with the mismatch negativity system.

The mismatch negativity (MMN), a component of event-related potentials (ERP), was used to investigate the effect of attention on auditory stream segregation. Subjects were presented with sequences of alternating high and low tones that occurred at a constant rate, which they ignored. When subjects ignored the stimuli, the three-tone standard and deviant sequences contained within the high- and low-pitched tones did not emerge and no MMNs were obtained. Subjects were then instructed to attend to the high-pitched tones of the stimulus sequences and detect the within-stream deviants. When subjects selectively attended the high-pitched tones, MMNs were obtained to the deviants within both the attended and unattended streams. These results indicate that attention can produce segregation such that the sequences of low- and high-pitched tones are available to the automatic deviance detection system that underlies the generation of the MMN. Selective attention can alter the organization of sensory input in the early stages of acoustic processing.

Speech evoked activity in the auditory radiations and cortex of the awake monkey.

To determine whether phonetic features of human speech are reflected in activity patterns of the auditory cortex and its thalamic afferents, concurrent recordings of multiple unit activity (MUA) and averaged evoked potentials (AEP) to 3 synthetic syllables: /da/,/ba/ and /ta/, were performed in awake monkeys. Using clicks, responses from thalamocortical axons and cortical cells were differentiated on the basis of their response latency, spatial distribution, and relationships to AEP components. Voice onset time was reflected in MUA time-locked to consonant release and voicing onset, and phase-locked to the syllables' fundamental frequency. Place of articulation was reflected in discriminative 'on' and phase-locked responses occurring to the formant transitions of the syllables. Duration of the voiced formant transitions was represented by an accentuation of the phase-locked responses occurring to this period. Activity of thalamocortical fibers and cortical cells differed. Thalamocortical fibers were more responsive to speech sounds, as well as responding more frequently with a phase-locked response pattern. Cortical cells responded with sustained activity to a greater degree. Responses to identical portions of the vowels were biased by the preceding consonant. The spatial extent and timing of the responses demonstrate that speech sounds are processed along parallel, but not synchronous, channels. Relevance to human psychoacoustical phenomena is discussed.